Members of the fibroblast growth factor (FGF) family play a quintessential role in cell growth and differentiation in a variety of tissues. We have identified cDNAs encoding four novel factors, from a human retinal cDNA library, with homology to HFS. The factors were named fibroblast growth factor homologous factors (HFS). Because of their preferential expression in the retina, these novel factors may be important in ocular physiology, pathophysiology and therapeutics. The primary aim of this proposal is to elucidate the biological function of these molecules through generation of mice with targeted disruption of HFS, and to compare the anatomic and physiologic features of FHF-null and wildtype mice by in-situ hybridization, immunohistochemistry, cell proliferation and programmed cell death assays, and electrophysiologic studies. A secondary aim is to determine the chromosomal locations of the four FHF structural genes in the human and mouse genomes, to identify human disease candidates or mouse mutant candidates, and to screen selected mutant mouse lines for FHF mutations.